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HIV Meets Oncology: An HIV Clinician’s View
Merceditas S. Villanueva MD
Director, HIV/AIDS Program
Yale University School of Medicine
HIV and Cancer Retreat
April 30, 2019
Case Presentation
• 58 year old man diagnosed with HIV in 1996
• Early years: serial ART mono and dual therapy with multidrug resistance
• Moved to CT 2005-worked in pharmaceutical field (ART development)
• I met him in 2009-applying for disability
ART Over Time
1985 1990 1995 2000 2005 2010 2015 2018
Zidovudine
Lamivudine
Didanosine
Stavudine
Nelfinavir
Saquinavir
Ritonavir
Tenofovir
Nevirapine
Efavirenz
Lopinavir+Ritonavir
Abacavir Fosemprenavir
EnfuvirtideIndinavir
Maraviroc
Rilpivirine
Raltegravir
Dolutegravir
Elvitegravir
Darunavir
Atazanavir
Etravirine
Emtricitabine
Tenofoviralafenamide
DoravirineIbalizumab
’82
“AIDS”
’83 Virus
isolation
’85
First
HIV
test
’87 AZT
approved
1981
AN AIDS TIMELINE: The 1st DecadeGEORGE H.W. BUSH
1989-1993
RONALD REAGAN
1981-1989
’96 HIV
viral load
approved
AIDS
Deaths
down
40% due
to
HAART
AN AIDS TIMELINE: The 2nd Decade
19901 1994 1995
WILLIAM CLINTON
1993-2000
Red
Ribbon
Tony
Awards
92’ ddl/ddC 93’ d4t Dual NRTI’s HAART ’97: NEL, DLV, Combivir
’95: Saquinavir ’96: NVP, IDV, RIT
GEORGE H.W. BUSH
1989-1993
’92 AIDS
leading cause
of death
adults 25-44
yrs old
‘96 My Pt was diagnosed HIV+
25
years30
years
’00 13th
Int’l AIDS
Conf in
Durban SA
PEPFAR:
$15B/5 yrs
2000
’00
Trizivir
Lopinavir
’01
Tenofo
vir
’03
Fuzeon
‘04
Truvada
’05
Tipranavir
‘06 Darunavir
-Atripla
’07
Maraviroc
Raltegravir
’08
Etravirine
AN AIDS TIMELINE: THE 3rd Decade …
GEORGE W. BUSH
2001-2008
BARACK H. OBAMA
2009 - 2016
’10 ACA passed
’12 IAS Conf
Wash DC
2010
'14
Elvitegr
avir
Triumeq
’16
Descovy,
Odefsey
’17
Juluca
’18
Biktarvy,
Delstrigo,
Pifeltro,
Ibalizumab
’13
Dolutegravir’15
Evotaz,
Genvoya,
Prezista
’11 RPV,
Complera
’12 Stribild
AN AIDS TIMELINE: THE 4th Decade …
BARACK H. OBAMA
2009 - 2016
DONALD J. TRUMP
2016-?
'19
Dovato
Back to Patient:Medical Problems Timeline
HIV
-Salvage regimen; multiple regimens with sequential
resistance and multiple side effects
Diabetes:
-Initially insulin requiring then Glipizide, Actos,
Metformin
Hyperlipidemia:
-Fibrate, Rosuvastatin, Lovaza
Hypercoaguable due to homocysteinemia (DVT, PE)
-Coumadin
Subdural hematoma
Hypothyroid
Depression
2009
Tenofovir/FTC/
Raltegravir/
Maraviroc
2014
MSSA
bacteremia/sepsis
intubated,
persistent throat
pain
Large 3.5 x 3.5 cm ulcerating mass centered
in the region of the left vallecula and involving
the left hyoglossus, genioglossus and
geniohyoid muscles. The mass is seen to
cross the midline and involve the median
glossoepiglottic fold and also the extrinsic
muscles of the tongue.
1996
Pathology
TONGUE, LEFT BASE, BIOPSY:
- SQUAMOUS CELL CARCINOMA, PREDOMINATELY NON-
KERATINIZING TYPE, WITH NECROSIS
• Immunohistochemistry:
p16 STRONGLY AND DIFFUSELY POSITIVE (>90% tumor cells)
Interpretation
Strong expression of p16 protein in head and neck squamous cell carcinomas is
associated with favorable prognosis, better response to radiation therapy, and HPV
related cancers
Oncologic Timeline
Dx
10/20-
12/8/149/2014
CRT with
Cetuximab
New
cervical
LN; FNA
metastatic
CA
7-9/2015
L MRND
9/201510/21-
11/24/15
ChemoRT
carboplatin
Hilar LN,
axillary LN,
RUL nodule,
right chest
wall: met CA
4-8/2016 8/15/16-
2/10/17
Pembroli
zumab
pneu
monitis
3/27-
5/22/17
Cetuximab/
carboplatinDEATH
(outside
hospital)
Progression of Disease and Outcomes
Pt. died 3 years and 8 months after cancer diagnosis
Just prior to death, CD4=284 cells/ul and HIV viral load <20 copies/ml
Challenges for HIV Physicians
• Medical knowledge expansion:
– New vocabulary:
• Cetuximab=EGFR inhibitor
• Pembrolizumab=antiPD-1 receptor (checkpoint inhibitor)
– Natural history
• p16
– Side effects, drug-drug interactions
• Multiple medical consultations overwhelming
– Serve as “translator” for patient as primary care anchor
• Keeping track given complexity of care
– Hospital admissions
– Test results
• Increasingly being “out of the loop” for major decisions made
Challenges for Patients
• Making and keeping track of many appointments
– Patients with less health literacy find it nearly impossible and get lost to care
• During hospitalizations, confusion about their medications and goals of care
– Admissions to Smilow, EP, MICU
• Who is quarterbacking their care?
– Goals of care decisions: oncology? HIV?
• Ongoing stigma about their HIV status
Reflections
• Lots of options to treat HIV and relatively easy to suppress with current ART
• As our patients age, increasing new problems not obviously related to HIV
– Need for HIV clinicians to gain mastery new clinical domains
– Need to “interpret” for patients complex series of medical
• It is exceeding challenging for our patients to navigate the medical world outside of their HIV “sheltered” world
• SHOULD WE CREATE A NEW PARADIGM FOR INTEGRATED CARE WITH ONCOLOGY AND HIV PROVIDERS?
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